| First Author | Ma T | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 426 |
| Issue | 2 | Pages | 196-202 |
| PubMed ID | 22935417 | Mgi Jnum | J:189965 |
| Mgi Id | MGI:5447590 | Doi | 10.1016/j.bbrc.2012.08.062 |
| Citation | Ma T, et al. (2012) Mitochondrial modulation of store-operated Ca(2+) entry in model cells of Alzheimer's disease. Biochem Biophys Res Commun 426(2):196-202 |
| abstractText | Mitochondrial malfunction and calcium dyshomeostasis are early pathological events considered as important features of the Alzheimer's disease (AD) brain. Recent studies have suggested mitochondrion as an active regulator of Ca(2+) signaling based on its calcium buffering capacity. Herein, we investigated the mitochondrial involvement in the modulation of store-operated calcium entry (SOCE) in neural 2a (N2a) transgenic AD model cells. Results showed that SOCE was significantly depressed in N2a cells transfected with wild-type human APP695 (N2a APPwt) compared with empty vector control (N2a WT) cells. Pharmacological manipulation with mitochondrial function blockers, such as FCCP, RuR, or antimycin A/oligomycin, could inhibit mitochondrial calcium handling, and then impair SOCE pathway in N2a WT cells. Furthermore, mitochondria of N2a APPwt cells exhibited more severe swelling in response to Ca(2+), which is an indication of mitochondrial membrane permeability transition (MPT), than the wild-type controls. Additionally, treatment with cyclosporin A, a potent inhibitor of cyclophilin D, which can block MPT, could significantly restore the attenuated SOCE in N2a APPwt cells. Therefore, inhibition of cyclophilin D might be a therapeutic strategy for Alzheimer's disease. |
